ultrasound enhanced delivery of molecular imaging and therapeutic agents in alzheimers disease mouse models增强超声分子成像和治疗制剂在阿尔茨海默病小鼠模型.pdfVIP

Ultrasound Enhanced Delivery of Molecular Imaging and Therapeutic Agents in Alzheimer’s Disease Mouse Models 1,2 1,3 4 3 5 Scott B. Raymond , Lisa H. Treat , Jonathan D. Dewey , Nathan J. McDannold , Kullervo Hynynen , Brian J. Bacskai2* 1The Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts, United States of America, 2 Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 3 Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 4 Duke University School of Medicine, Durham, North Carolina, United States of America, 5 Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada Abstract Alzheimer’s disease is a neurodegenerative disorder typified by the accumulation of a small protein, beta-amyloid, which aggregates and is the primary component of amyloid plaques. Many new therapeutic and diagnostic agents for reducing amyloid plaques have limited efficacy in vivo because of poor transport across the blood-brain barrier. Here we demonstrate that low-intensity focused ultrasound with a microbubble contrast agent may be used to transiently disrupt the blood-brain barrier, allowing non-invasive, localized delivery of imaging fluorophores and immunotherapeutics directly to amyloid plaques. We administered intravenous Trypan blue, an amyloid staining red fluorophore, and anti-amyloid antibodies, concurrently with focused ultrasound therapy in plaque-bearing, transgenic mouse models of Alzheimer’s disease with amyloid pathology. MRI guidance permitted selective treatment and monitoring of plaque-heavy anatomical